EP0497240B1 - Preparation for controlled release of drugs for ruminants - Google Patents

Abstract

The invention relates to a composition which contains at least one active substance, a wax, a weighting agent and optionally a sugar, sugar alcohol, cellulose ether or a polyethylene glycol, an active substance release system built up from this composition, a process for its preparation and its use in veterinary medicine and animal nutrition.

Description

Shaped product for the controlled release of active ingredients that are used as therapeutic agents or to improve growth and feed conversion in ruminants are suitable

The invention relates to a molding which has at least one active ingredient, a wax Weighting agents and possibly a sugar, sugar alcohol, Contains cellulose ether or a polyethylene glycol, a process for its manufacture and Use in veterinary medicine and animal nutrition.

Drug release systems are preparations that contain one or more (Physiologically) active ingredients in a defined release profile via a Release the set time in a controlled manner.

1) Therapie im engeren Sinn, d.h. die Kontrolle parasitärer Infektionen und/oder Erkrankungen, sowie im weiteren Sinne auch

2) die Zufuhr von Mangelstoffen (z.B.: Spurenelemente),

3) die Steuerung metabolischer Prozesse (z.B.: Leistung),

4) die Steuerung endokriner Vorgänge (z.B.: Fertilität).

The main areas of indication for the use of these systems in veterinary medicine are:

1) Therapy in the narrower sense, ie the control of parasitic infections and / or diseases, as well as in the wider sense

2) the supply of deficient substances (e.g. trace elements),

3) the control of metabolic processes (e.g.: performance),

4) the control of endocrine processes (e.g. fertility).

Indications for the use of these systems in animal nutrition are especially the improvement of growth and feed conversion Ruminating.

Advantages of drug delivery systems compared to conventional ones Dosage forms are an optimal active ingredient level during the whole Duration of use, a lower dosage of active ingredient, a working and therefore ultimately cost savings for the pet owner.

The disadvantages that may arise, such as the development of resistance or Habituation, drug residues and waiting time, tissue irritation and whereabouts of a foreign body after the end of use can and must be replaced by a optimal galenic development excluded or at least clearly be minimized.

Active ingredient delivery systems for oral administration in ruminants, hereinafter referred to as "boluses", are described in detail in the specialist literature (for example Formulation of Veterinary Dosage Forms, by Jack Blodinger, Marcel Dekker Inc. New York, 1983). The location of the bolus in the gastro-tract of the animal is caused by the geometric shape or by the density of the system. In the latter case one speaks of a "high density device" (HDD). It is known from the literature that HDD should have a density> 2 g / cm ³ (J. Riner et al., Am. J. Vet. Res. 43 (1982), pp. 2028-2030), so that the bolus despite the natural regurgitation of the ruminant cannot be choked out again.

The "high density devices" described so far are therefore provided with a weight element in order to achieve the required overall density. This weight element is preferably used as a solid metal block, for example EP-A-0 333 311, EP-A-0 149 510, EP-A-0 062 391 or as a cylinder, for example EP-A-0 164 241 and Vet. Parasitology 12 (1983) 223-232 executed. These metal elements described in the literature have the disadvantage that they are not biodegradable and remain as foreign bodies in the animal's stomach beyond the desired duration of application. Adverse consequences of this include interactions with other bolus systems with multiple applications, irritation of the mucous membranes and problems with slaughtering and cutting up the animals.

Use offers some progress in overcoming these drawbacks degradable weight elements as described in EP-A-0 332 094. However the systems described there are still not optimally suited. You are from composed of several very different components. This Components include a) a mixture (matrix) of a degradable polymer and active ingredient, b) a mixture (matrix) of a degradable polymer and High density particles, c) a degradable polymer and d) high density particles.

The disadvantage is the complex structure of the systems, which is usually a separate one Production with subsequent assembly of the individual parts required. The maximum amount of active ingredient to be administered is due to the limited volume of the degradable polymer severely restricted. It should also be noted that Degradation of the different polymers or due to mechanical influences in the Gastrotract can easily separate the individual parts of the system. The bolus systems described therefore only correspond to the restrictions Practical requirements in manufacturing and therapeutic safety.

Finally, in EP-A-0 243 111. Bolus systems described that are made up of molded articles that contain an iron granulate in addition to the active ingredient and Contain graphite as well as a cover made of magnesium alloy and a protective cover made of non-degradable plastic. Magnesium, iron and graphite form in Gastric juice is a galvanic element that corrodes the magnesium shell causes. In this way, the drug release is controlled.

The disadvantage of this system is the simultaneous release of magnesium ions. Magnesium is a physiologically active substance and is used in the Veterinary medicine as a drug, e.g. against grass tetany in calves.

The manufacture of the above-mentioned bolus systems is comparatively complex and expensive. Pressing the iron granules into the moldings causes a considerable abrasion of the pressing tools used. The resulting short downtimes lead to an increase in production costs. The The use of a non-degradable plastic is not without problems, since the Plastic either as a foreign body in the animal after the bolus has expired remains or is excreted and pollutes the environment.

1) einfache, sichere Applizierbarkeit,

2) vollständige Retention am Wirkort während der gesamten Dauer der Wirkstofffreisetzung,

3) kontrollierte Wirkstoff-Freisetzung mit klarem Endpunkt,

4) keine unerwünschten Nebenwirkungen und keine Gewebeschäden,

5) kein verbleibender Fremdkörper nach Abschluß der Behandlung.

A practical bolus system should meet the following requirements:

1) simple, safe applicability,

2) complete retention at the site of action during the entire period of drug release,

3) controlled release of active substance with a clear end point,

4) no undesirable side effects and no tissue damage,

5) no foreign body remaining after completion of the treatment.

Surprisingly, these requirements are met by a bolus system in which the bolus preparation consists of the active ingredient, a non-water-soluble paraffin or wax, a substance which influences the mechanical properties of the preparation, in particular abrasion and / or decay, if appropriate a surface-active substance and a powdery substance of high density (> 3 g / cm ³ ).

The present invention therefore relates to a Form for oral application in ruminants, containing 0.001 to 75% by weight of at least one active ingredient, 3 to 75% by weight wax, 25 to 90% by weight of powdered weighting agent and 0 to 30% by weight at least one physiologically compatible sugar, sugar alcohol, water-soluble cellulose ether or polyethylene glycol can be produced by mixing the components of the molding in a mixer in this way that the heat of friction leads to the formation of a melt granulate, which is pressed into a molding after cooling without further melting.

The molding preferably contains up to 50% by weight, in particular up to 30% % By weight of at least one active ingredient, preferably 5 to 60% by weight, in particular 5 to 50% by weight of wax, preferably 30 to 85% by weight, in particular 40 to 80 wt .-% powdered weighting agent and preferably 0 - 14% by weight, in particular 0 - 10% by weight at least one physiologically compatible sugar, sugar alcohol, water-soluble cellulose ether or polyethylene glycol, or a mixture thereof.

If an active ingredient is not or only slightly soluble in water (e.g. Fenbendazole), it is beneficial to increase the sugar, sugar alcohol, water-soluble cellulose ether or polyethylene glycol not less than 1% by weight reduce. A content of 1.5 to 27% by weight, in particular 2 to 25% by weight.

The molding may also contain up to 8% by weight, preferably up to 6% % By weight of a surfactant, up to 10% by weight, preferably up to 6 % By weight mold release agent, a lubricant and / or substances which the Affect the properties of the preparation.

Ruminants are understood to mean in particular cattle, sheep and goats.

The therapeutic agents are in particular agents to control parasitic infections and / or diseases, to supply Deficiency substances, to control metabolic processes or to control endocrine processes.

• Glucocorticoide zur Geburtsinduktion, z.B. Dexamethason, Betamethason, Flumethason, deren Ester und Derivate,
• Gestagene zur Brunstsynchronisation, Brunst- und Läufigkeitsunterdrückung,
• β₂-Adrenergika zur Therapie und Prophylaxe von Respirationserkrankungen, zur Verhinderung von Abort und Geburt, zur Wachstumsförderung und Stoffwechselbeeinflussung, wie z.B. Clenbuterol, 4-(2-tert.-Butylamino-1-hydroxyethyl)-2-cyano-6-fluor-phenylcarbaminsäure-ethylester-hydrochlorid, α[[[3-(1-Benzimidazolyl)-1,1-dimethylpropyl]-amino]-methyl]-2-fluor-4-hydroxybenzyl alkohol-methansulfonat monohydrat (Cimaterol), 1-(4-Amino-3-cyanophenyl)-2-iso-propylaminoethanol,
• β-Blocker zur Reduzierung von Transport-Stress, α₂-Adrenergika gegen enteritische Erkrankungen und zur Behandlung hypoglykämischer Zustände, sowie zur Sedation (z.B. Clonidin), 2-[2-Brom-6-fluorphenylimino]-imidazolidin,
• Benzodiazepine und Derivate, wie z.B. Brotizolam zur Sedation,
• Antiphlogistika zur antiinflammatorischen Therapie, z.B. Meloxicam
• Endorphine zur Anregung der Pansenmotorik,
• Steroidhormone (natürliche und synthetische) zur Wachstumsförderung, z.B. Östradiol, Progesteron und deren Ester und synthetische Derivate wie z.B. Trenbolon,
• Antiparasitika zur Bekämpfung von Endo- und Ektoparasiten, wie z.B. Levamisol, Avermectin, Benzimidazole, Pyrantel, Morantel, Febantel,
• herz- und kreislaufaktive Substanzen, z.B. Etilefrin oder Pimobendan.

According to the invention, for example, the therapeutically active substance groups and compounds mentioned below can be used in the molding.

• Glucocorticoids for induction of childbirth, e.g. dexamethasone, betamethasone, flumethasone, their esters and derivatives,
• Progestogens for heat synchronization, heat and heat suppression,
• β ₂ -adrenergics for the therapy and prophylaxis of respiratory diseases, for preventing abortion and childbirth, for promoting growth and influencing the metabolism, such as clenbuterol, 4- (2-tert.-butylamino-1-hydroxyethyl) -2-cyano-6-fluoro- phenylcarbamic acid ethyl ester hydrochloride, α [[[[3- (1-benzimidazolyl) -1,1-dimethylpropyl] amino] methyl] -2-fluoro-4-hydroxybenzyl alcohol methanesulfonate monohydrate (cimaterol), 1- (4th -Amino-3-cyanophenyl) -2-iso-propylaminoethanol,
• β-blocker to reduce transport stress, α ₂ -adrenergics against enteric diseases and for the treatment of hypoglycemic conditions, as well as for sedation (eg clonidine), 2- [2-bromo-6-fluorophenylimino] imidazolidine,
• Benzodiazepines and derivatives, such as breadizolam for sedation,
• Anti-inflammatory drugs for anti-inflammatory therapy, eg meloxicam
• Endorphins to stimulate rumen motor skills,
• Steroid hormones (natural and synthetic) for promoting growth, for example estradiol, progesterone and their esters and synthetic derivatives such as trenbolone,
• Antiparasitics for combating endoparasites and ectoparasites, such as, for example, levamisole, avermectin, benzimidazoles, pyrantel, morantel, febantel,
• cardiovascular active substances, e.g. Etilefrin or Pimobendan.

Ia), worin

R¹

Methoxycarbonylamino bedeutet und

R²

n-Propylmercapto (Albendazol), Phenylmercapto (Fenbendazol), Phenylsulfinyl (Oxfendazol), Benzoyl (Mebendazol), p-Fluorbenzoyl (Flubendazol), p-Fluorphenylsulfonyloxy (Luxabendazol), Cyclopropylcarbonyl (Cyclobendazol), n-Butyl (Parbendazol), n-Propoxy (Oxibendazol) oder H (Carbendazim) bedeutet oder

Ib), worin

R¹

4-Thiazolyl bedeutet und

R²

H (Thiabendazol) oder Isopropoxycarbonylamino (Cambendazol).

Active substances from the group of the benzimidazole, benzothiazole derivatives or the pro-benzimidazoles, in particular compounds of the formulas I, II or III, are preferred

Ia), in which

R ¹

Methoxycarbonylamino means and

R ²

n-propylmercapto (albendazole), phenylmercapto (fenbendazole), phenylsulfinyl (oxfendazole), benzoyl (mebendazole), p-fluorobenzoyl (flubendazole), p-fluorophenylsulfonyloxy (luxabendazole), cyclopropylcarbonyl (cyclobendazole), n Propoxy (oxibendazole) or H (carbendazim) means or

Ib), in which

R ¹

4-thiazolyl means and

R ²

H (thiabendazole) or isopropoxycarbonylamino (cambendazole).

II.

R³

Methoxycarbonylamino bedeutet und

R⁴

n-Propoxy bedeutet, (Tioxidazol).

wherein

R ³

Methoxycarbonylamino means and

R ⁴

n-propoxy means (tioxidazole).

III.

R⁵

-N=C(NHCOOCH₃)₂,

R⁶

-NHCOCH₂OCH₃,

R⁷

Phenylmercapto und

R⁸

H bedeuten (Febantel); oder

R⁵

R⁶

NO₂, R⁷ H und R⁸ n-Propylmercapto bedeuten (Netobimin); oder

R⁵ und R⁶

jeweils -NHCSNH-COOC₂H₅, R⁷ und R⁸ jeweils H bedeuten (Thiophanat).

wherein

R ⁵

-N = C (NHCOOCH ₃ ) ₂ ,

R ⁶

-NHCOCH ₂ OCH ₃ ,

R ⁷

Phenylmercapto and

R ⁸

H mean (Febantel); or

R ⁵

R ⁶

NO ₂ , R ⁷ H and R ^{8 represent} n-propylmercapto (netobimin); or

R ⁵ and R ⁶

each represents -NHCSNH-COOC ₂ H ₅ , R ⁷ and R ⁸ each denote H (thiophanate).

Fenbendazole is particularly preferred.

To improve growth and feed conversion in ruminants can, for example, the substance groups and compounds mentioned below be used in the molding according to the invention.

Salinomycin, flavophospholipol, monensin, dehydromethylmonensin, narsin, Deoxynarsin, lasalocid A, alborixin, lysocellin, nigericin, Dehydroxymethylnigericin, dianemycin, ionomycin, norbitomycin and others Polyether antibiotics, avoparcin, spiramycin, tylosin, virginiamycin, bacitracin A, Carbadox, nitrovin, olaquindox, amprolium, arprinacid, dinitolmid, halofuginone, Metichlorpindole, nicarbazine, decoquinate, triazine derivatives and the salts of mentioned compounds such as salinomycin-Na, monensin-Na, tylosin phosphate, Zn-bacitracin A, Lasalocid A-Na.

Phospho-glycolipids, in particular flavophospholinol, are particularly preferred. Salinomycin and its salt, preferably Na salt.

A wax in the sense of the present invention means one physiologically harmless naturally or artificially obtained substance which has the following properties: solid to brittle hard at room temperature, rough to fine crystalline, translucent to opaque, but not glassy; over 40 ° C without Melting decomposition, already a little above the melting point relatively low viscosity and non-stringy, strongly temperature-dependent Consistency and solubility.

From similar synthetic or natural products (e.g. resins, plastic Masses) they differ mainly in that they are usually about melt between 50 and 90 ° C. Suitable are e.g. recent waxes, like Candelilla, carnauba wax, and fossil waxes such as montan wax, etc., Mineral waxes such as ceresin, ozokerite (earth wax),

Petrolatum, paraffin and micro waxes; chemically modified waxes are e.g. the Hoechst and BASF waxes produced by oxidation of raw montan wax and hydrogenated jojoba oil or castor oil (e.g. Cutina HR) as well as synthetic Waxes (synthetic waxes).

The powdered weighting agent is to be selected with regard to its specific density, its composition and its quantity so that the bolus system remains in the stomach despite the natural regurgitation. Depending on the size of the bolus system and its surface, the specific density, depending on the composition of the sealing part, is generally greater than 3.0 g / cm ³ , preferably greater than 4.0 g / cm ³ .

Upward, density is not a limiting criterion.

Examples are weighting agents that have a sufficiently high density: Weighting means Density (g / cm ³ silver 10.5 copper 8.9 iron 7.8 nickel 8.9 lead 11.3 antimony 6.7 tin 7.3 zinc 7.1 Hydroxyapatite 3.1-3.3 Barium sulfate 4.5 Iron oxides 5.2-5.7 Barium titanate 6.1 Alumina 4.0 Tin oxide 7.0 Titanium dioxide (rutile) 4.2 Scheelite (calcium tungstate 6.1 Ferberite (iron tungstate) 7.2 Fayalite (iron silicate) 4.4 Hercynite (iron aluminum oxide) 4.3 Powellit (calcium molybdate) 4.3 Calcium phosphates 4.3

Non-toxic substances such as barium sulfate or are preferably used Iron powder, especially iron powder.

For substances with a high specific density, particle sizes are smaller than 1 mm, possibly also less than 0.1 mm preferred. This is the case with the invention used iron powder 97% of the particles ≤ 0.15 mm, 80% ≤ 0.1 mm.

In the case of water-soluble active ingredients, the proportion of sugar, sugar alcohol, water-soluble cellulose ether or polyethylene glycol can be reduced, or these Auxiliaries can be omitted entirely.

Suitable sugars according to the invention are, for example, water-soluble pharmaceutically acceptable monosaccharides and disaccharides. Is preferred Lactose, but glucose, fructose, xylose, galactose, sucrose, Maltose and related compounds such as mannitol, xylitol, sorbitol.

Suitable water-soluble cellulose ethers are the ®Tylose brands ®Tylose MB (Methyl cellulose) and ®Tylose H (hydroxyethyl cellulose), is preferred Methyl cellulose.

Polyethylene glycols (PEG) in the sense of the present invention are e.g. PEG 400, 600, 1500, 2000, 3000, 4000, 6000 and 10000. The fixed types are preferred.

Physiologically compatible are preferred as surface-active substances non-ionic surfactants with an HLB value between 10 and 20, especially those Polyoxyethylene sorbitan esters, such as the monolaurate (®Tween 20), the monopalmitate (®Tween 40) and the monostearate (®Tween 60) in question. ®Tween 20 is preferred.

Talc and stearates are usually used as lubricants and mold release agents or other metal soaps, such as fumarates or palmitates, are preferred Magnesium stearate.

As an adjuvant, the mechanical properties, especially abrasion and Decay, which can influence, is usually highly disperse silicon dioxide (®Aerosil) used.

The invention further relates to moldings for oral application in ruminants consisting of an agent defined above, which one for a defined Release of a sufficient amount of the active substance for a set time contains, and one soluble or degradable in the digestive tract Cover.

The present invention further relates to a Process for producing a molding as described above, characterized in that one from the components of the molding in a suitable mixer Exploitation of the frictional heat Melt granules that after cooling without further melting into one Molding is pressed.

The molding or the individual moldings have a diameter depending on the animal species, which is between 1 cm and 4 cm. The total length of the bolus should not be 12 cm exceed, the lower limit is a single tablet. The molding can one piece (Fig. 1) or any number of individual pieces (Fig. 2 and 3) exist.

The total volume can thus be between about 0.5 and 200 cm ³ .

By increasing the surface, i.e. by transition from one piece (Fig. 1) to the tablet form (Fig. 2, 3), the release rate can be the same Composition of the matrix can be increased and depending on the number, size and Shape of the moldings to be adapted to the requirements. The loss of individuals Moldings during the treatment period, e.g. through regurgitation, it prevents by connecting the tablets together. This connection can flexible, e.g. by a band, a thread or a chain, elastic or rigid, e.g. by a rod, (Fig. 2, 3). The connecting material can, for example made of physiologically harmless plastic (e.g. silicone) or one physiologically harmless material that is broken down in the intestine.

A tablet tablet (Fig. 2, 3) also avoids the risk of the matrix can break or be damaged by external influences. This is how one becomes Guaranteed more even release throughout the application period.

The height of the moldings can depend on the desired release profile of the Active ingredient vary. Various tablet forms are also available, e.g. biplane, biconvex, possible. Shapes of different shapes can also be used in one bolus Height and shape can be combined. It is also possible to use moldings those with an active ingredient in different concentrations or with different Active substances are loaded to combine with each other. To facilitate the Application, the interconnected moldings with the help of a water-soluble glue glued together or with one in the digestive tract soluble or degradable shell are surrounded. The material of the adhesive or the cover can e.g. from cellulose and cellulose derivatives, gelatin and other suitable polymers and copolymers. The moldings can also be surrounded by a network.

The products manufactured in the above-mentioned way can consist of up to 30, preferably up to 20, in particular up to 10 moldings. The matrix is completely broken down during the treatment period; a backlog remains Treatment did not return.

The drug release system described is basically suitable for Application of all active ingredients in the areas of veterinary medicine and Animal nutrition can be administered over a long period of time. Different physical properties of the active ingredients, e.g. Differences in solubility influenced by suitable additives that control the release of active ingredient will. Suitable additives to control the release profile according to the therapeutic requirements are known to the person skilled in the art.

The invention therefore also relates to the use of the above-mentioned moldings and ruminant products for the prophylaxis and / or treatment of Diseases and to influence growth, metabolism, Body weight, tissue composition and / or feed conversion.

The following examples serve to illustrate the invention without this would be limited to this.

B. General manufacturing example for a melt granulate

The ingredients of the formulation are placed in a suitable mixer (e.g. Weighing fluid mixer from Henschel). Because of the friction when mixing The heat generated leads to the formation of melt granules. After cooling of the granules at room temperature are agglomerates by passing over a Screen (e.g. Frewitt granulator, mesh size: 1 mm) crushed.

The granulate standardized in this way is then used to press the desired granules Moldings pressed. If necessary, a lubricant or mold release agent be added.

Wirkstoff: bis zu 30 %

Wachs: 5 - 50 %

Eisen: 40 - 80 %

Lactose, Methylcellulose oder Polyethylenglykol: 0 - 25 %

hochdisperses Siliziumdioxid: bis zu 2 %

Polyoxyethylen-Sorbitanmonolaurat: bis zu 6 %

Mg-Stearat: bis zu 6 %.

The preparations prepared according to A. or B. in the following examples preferably have the following composition (% data are% by weight):

Active ingredient: up to 30%

Wax: 5 - 50%

Iron: 40 - 80%

Lactose, methyl cellulose or polyethylene glycol: 0 - 25%

highly disperse silicon dioxide: up to 2%

Polyoxyethylene sorbitan monolaurate: up to 6%

Mg stearate: up to 6%.

Claims (19)

1. A molded article for oral administration in ruminants, containing 0.001 to 75% by weight of at least one active substance, 3 to 75% by weight of wax, 25 to 90% by weight of powdered weighting agent and 0 to 30% by weight of at least one physiologically tolerable sugar, sugar alcohol, water-soluble cellulose ether or polyethylene glycol, preparable by mixing the constituents of the molded article in a mixer in such a manner that the frictional heat leads to the formation of fused granules which are pressed to give a molded article after cooling without further melting.
2. A molded article as claimed in claim 1, which contains at least one surface-active substance, a lubricant, a mold release agent and/or a substance which affects the mechanical properties of the preparation.
3. A molded article as claimed in claim 1 or 2, wherein the weighting agent is iron powder.
4. A molded article as claimed in one of claims 1 to 3, wherein the active substance is an agent for the control of parasitic infections and/or diseases, for the supply of deficient substances, for the control of metabolic processes or for the control of endocrine processes.
5. A molded article as claimed in one of claims 1 to 3, containing at least one active substance for improving growth and/or the utilization of feed.
6. A molded article as claimed in one of claims 1 to 4, wherein the active substance is an anthelmintic, preferably from the active substance group comprising benzimidazole and benzothiazole derivatives or the probenzimidazoles.
7. A molded article as claimed in claim 6, containing the active substance fenbendazole.
8. A molded article as claimed in one of claims 1 to 3 and 5, wherein the active substance is a polyether antibiotic.
9. A molded article as claimed in one of claims 1 to 3 and 5, wherein the active substance is a phosphoglycolipid.
10. A molded article as claimed in one of claims 1 to 3 and 5, containing the active substance salinomycin or its salt.
11. A molded article as claimed in claim 9, wherein the active substance is flavophospholipol.
12. A molded article for oral administration in ruminants as claimed in one of claims 1 to 11, which contains an adequate amount of the active substance for defined release during a fixed period, and optionally a coating which is soluble or can be degraded in the digestive tract.
13. A product containing a plurality of molded articles as claimed in claim 12.
14. A product as claimed in claim 13, wherein the molded articles are connected to one another by means of a tape, a thread, a chain, a rod, or by bonding or inclusion in a net.
15. A product as claimed in claim 13 or 14, which is composed of molded articles of varying dimension and shape, a different content of active substance and/or different type of active substance.
16. A product as claimed in one of claims 13 to 15, whose total volume is between 0.5 and 200 cm³.
17. A process for the preparation of a molded article as claimed in one of claims 1 to 11, which comprises preparing fused granules from the constituents of the molded article in a suitable mixer with utilization of the frictional heat, which fused granules are pressed to give a molded article after cooling without further melting.
18. A process for the preparation of molded articles as claimed in claim 12, fused granules prepared as claimed in claim 17 comminuting and pressing them to give the desired molded articles using a press and providing the molded articles thus obtained with a coating which is soluble or can be degraded in the digestive tract.
19. A molded article as claimed in claim 12 or a product as claimed in one of claims 13 to 16 for the prophylaxis and/or for the treatment of diseases in ruminants.

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